Efficacy, retention and tolerability of everolimus in patients with tuberous sclerosis complex: a survey-based study on patients’ perspectives

Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) re
Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. Objective: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective. Methods: A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC. Results: Of 365 participants, 36.7% (n = 134) reported the current or past intake of EVE, including 31.5% (n = 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m2 (median: 5.6 mg/m2, range 2.0–15.1 mg/m2) in children and adolescents and 4 ± 2.1 mg/m2 (median: 3.7 mg/m2, range 0.8–10.1 mg/m2) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE. Conclusions: From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.
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Author:Laurent Maximilian Willems, Felix Rosenow, Susanne Schubert-Bast, Gerhard Kurlemann, Johann Philipp Zöllner, Thomas Bast, Astrid Bertsche, Ulrich Bettendorf, Daniel Ebrahimi-Fakhari, Janina Grau, Andreas Hahn, Hans Hartmann, Christoph Hertzberg, Frauke Hornemann, Ilka Immisch, Julia Jacobs-LeVan, Karl Martin Klein, Kerstin Alexandra Klotz, Gerhard Kluger, Susanne Knake, Markus Knuf, Klaus Marquard, Thomas Mayer, Sascha Meyer, Hiltrud Muhle, Karen Müller-Schlüter, Felix von Podewils, Susanne Ruf, Matthias Sauter, Hannah Schäfer, Jan-Ulrich Schlump, Steffen Syrbe, Charlotte Thiels, Regina Trollmann, Adelheid Wiemer-Kruel, Bernd Wilken, Bianca Zukunft, Adam Strzelczyk
Parent Title (English):CNS drugs
Place of publication:Berlin [u.a.]
Document Type:Article
Date of Publication (online):2021/07/17
Date of first Publication:2021/07/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/16
First Page:1107
Last Page:1122
Open Access funding enabled and organized by Projekt DEAL. This work was supported by the federal state Hessen with a LOEWE grant to the Center of Personal and Translational Epilepsy Research (CePTER).
HeBIS PPN:494572469
Dewey Decimal Classification:610 Medizin und Gesundheit
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0

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